Drug-induced weight gain is a clinically important adverse event that can lead to obesity, metabolic syndrome, cardiovascular disease, and reduced treatment adherence. Although several drug classes are known to cause weight gain, the onset timing and underlying mechanisms remain incompletely understood. This study aimed to investigate signals and evaluate time to onset of drug-induced weight gain using the Japanese Adverse Drug Event Report (JADER) database. We analyzed JADER data from April 2004 to June 2025, and in the disproportionality analysis reporting odds ratios with 95% confidence intervals were calculated. Time to onset was also assessed, and Weibull distribution analysis was applied to evaluate onset patterns. Among 975,869 reports, 814 cases of drug-induced weight gain were identified. Signals were detected for known drugs such as antipsychotics, pregabalin, and pioglitazone, as well as for drugs without weight gain listed in their package inserts, including benzodiazepines. Pregabalin showed the earliest median onset at 19 days (early failure), followed by olanzapine and risperidone at 1-2 months, pioglitazone at 2 months, and clozapine at 6 months, all classified as random failure types. This study demonstrated that drug-induced weight gain varies by drug class in both onset timing and mechanisms. These findings underscore the need for careful weight monitoring during treatment, particularly early with pregabalin and long-term with clozapine and pioglitazone. Prospective studies are warranted to clarify causal relationships and clinical implications.
Keywords: Japanese Adverse Drug Event Report database; Weibull distribution; disproportionality analysis; time to onset; weight gain.